Luteolin alleviates cerebral ischemia/reperfusion injury by regulating cell pyroptosis.

OBJECTIVE

This study aimed to clarify the roles and underlying mechanisms of luteolin in the progression of cerebral ischemia/reperfusion injury (CIRI).

METHODS

A mouse model of CIRI was established using the middle cerebral artery occlusion (MCAO) method, after which luteolin was administered. Subsequently, neuronal apoptosis and pyroptosis were measured and the brain tissues of each group were subjected to RNA sequencing.

RESULTS

Luteolin alleviated MCAO-induced brain infarction, apoptosis, and pyroptosis. RNA sequencing identified 3,379, 2,777, and 3,933 differentially expressed genes (DEGs) in the MCAO vs sham, MCAO vs MCAO + luteolin, and MCAO + luteolin vs sham groups, respectively. The identified DEGs showed enrichment in multiple processes, including pattern specification, forebrain development, anion transport, leukocyte migration, regulation of cell-cell adhesion, and positive regulation of the response to external stimuli, as well as the calcium, PI3K-AKT, JAK-STAT, NF-kappa B, IL-17, cAMP, cGMP-PKG, and Wnt signaling pathways. In addition, and interacted more with the other top 30 DEGs with high interaction weights. Finally, RT-qPCR results showed that MCAO induction significantly up-regulated the expression of , , and and down-regulated , , and ; however, luteolin could partially reverse the expression caused by MCAO.

CONCLUSION

Luteolin can alleviate brain infarction, apoptosis, and pyroptosis in CIRI, and may improve MCAO-induced CIRI by targeting the identified DEGs and their enriched pathways.